These investigations are directed towards examining the factors and mechanisms regulating the function and growth of the normal adrenal cortex as well as of tumors of the adrenal cortex. We will study certain properties of the adenylate cyclase of the normal and neoplastic adrenal cortex, including an examination of the influence of various hormones on cyclase activity (to date, only ACTH has been found to stimulate normal adrenal cyclase while other hormones influence tumor cyclase as well). Since certain adrenocortical cancers have been found to possess a cyclase responsive to other hormones as well as ACTH, we will study binding of the hormones to membrane preparations in an attempt to determine whether common or multiple receptor sites are involved. We will carry out studies to determine whether those hormones that influence adenylate cyclase activity of adrenocortical cancers also influence cyclic AMP levels and steroidogenesis in vivo as well as in tumor slices in vitro. We plan to study these questions in experimental animal tumors, and certain of these questions will also be approached in human adrenocortical tumors. Another line of investigation will involve inquiry into mechanisms by which cyclic AMP regulates steroidogenesis in the adrenal cortex. Abnormalities in the regulatory mechanism will be looked for in adrenal cortical tumors. Specifically we will address the question of whether cyclic AMP directly or through a protein kinase activates mitochondrial enzymes involved in conversion of cholesterol to delta5-pregnenolone or whether the regulated step involves making cholesterol available for these mitochondrial enzymes. Furthermore, we will carry out studies dealing with the mechanism of action of certain adrenal inhibitors. Since some of these compounds are inhibitors of protein synthesis, we will re-explore the question of the role of protein synthesis in the steroidogenic action of ACTH and cyclic AMP. We will examine mechanisms involved in the growth promoting action of ACTH. Lastly, we will look at the question of whether other nucleotides in addition to cyclic AMP are involved in the mechanism of action of ACTH.